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A national survey of the attitudes of physicians toward the selection of human growth hormone products and factors affecting physicians' prescribing decisions was conducted. A survey was mailed to 800 pediatric endocrinologists. Recipients were asked to rank eight qualities of human growth hormone therapy from a patient's perspective, to rate the importance of each of 15 factors to the prescribing of human growth hormone products, and to respond to a hypothetical clinical situation set up to assess opinions on the interchangeability of human growth hormone products. The physicians were also asked whether they thought all human growth hormone products were clinically equivalent and, if so, whether a formulary should be limited to one brand of product for all indications. The net response rate was 29%. Physicians ranked insurance coverage and out-of-pocket expenses as the most important factors from the patient's perspective and reported efficacy, patient comfort or compliance, insurance coverage, and drug cost as the most important factors to consider when selecting a human growth hormone product; patient preference was reported to be the least important. A total of 209 physicians (92%) considered all human growth hormone products to be clinically equivalent; not quite half of these favored limiting a formulary to one brand of product. Concerning the hypothetical situation, 210 of 226 (93%) respondents indicated that they would not switch all patients receiving one product (product A) to another product (product B) and 192 of 223 (86%) that they would not switch all patients receiving product B to product A. A national sample of pediatric endocrinologists agreed on the clinical equivalence of most human growth hormone products but not on limiting a formulary to one brand of product.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10048879&dopt=Abstract

J Biol Chem. 1999 Feb 26;274(9):5605-11.
Evidence for conservation of the vasopressin/oxytocin superfamily in Annelida.

Satake H, Takuwa K, Minakata H, Matsushima O.

Suntory Institute for Bioorganic Research, Wakayamadai 1-1-1, Shimamoto-cho, Mishima-gun, Osaka 618-8503, Japan.

Annetocin is a structurally and functionally oxytocin-related peptide isolated from the earthworm Eisenia foetida. We present the characterization of the annetocin cDNA. Sequence analyses of the deduced precursor polypeptide revealed that the annetocin precursor is composed of three segments: a signal peptide, an annetocin sequence flanked by a Gly C-terminal amidation signal and a Lys-Arg dibasic processing site, and a neurophysin domain, similar to other oxytocin family precursors. The proannetocin showed 37.4-45.8% amino acid homology to other prohormones. In the neurophysin domain, 14 cysteines and amino acid residues essential for association of a neurophysin with a vasopressin/oxytocin superfamily peptide were conserved, suggesting that the Eisenia neurophysin can bind to annetocin. Furthermore, in situ hybridization experiments demonstrated that the annetocin gene is expressed exclusively in neurons of the central nervous system predicted to be involved in regulation of reproductive behavior. These findings confirm that annetocin is a member of the vasopressin/oxytocin superfamily. This is the first identification of the cDNA encoding the precursor of an invertebrate oxytocin-related peptide and also the first report of the identification of an annelid vasopressin/oxytocin-related precursor.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10026177&dopt=Abstract

Toxicol Lett. 1998 Nov 23;100-101:233-8.
Functional characteristics of recombinant human GABA(A) receptors containing the epsilon-subunit.

Thompson SA, Bonnert TP, Whiting PJ, Wafford KA.

Neuroscience Research Centre, Merck Sharp & Dohme Research Laboratories, Harlow, Essex, UK.

(1) This paper further examines the functional characteristics of recombinant human GABA(A) receptors containing the epsilon-subunit expressed in Xenopus oocytes. (2) Alpha1beta1epsilon receptors are not modulated by benzodiazepine ligands or by a number of hypothalamic hormones. (3) The intravenous anaesthetic agents pentobarbital, propofol and etomidate all potentiate sub-maximal GABA currents (EC20) to a similar degree in alpha1beta1epsilon and alpha1beta1gamma2s receptors. (4) Direct activation by pentobarbital produced a similar maximum response on alpha1beta1epsilon and alpha1beta1gamma2s, however, both the EC50 and slope were lower on alpha1beta1epsilon compared to alpha1beta1gamma2s. (5) These results describe a novel pharmacology for recombinant alpha1beta1epsilon receptors.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10049148&dopt=Abstract

Hum Gene Ther. 1999 Jan 1;10(1):49-59.
Delivery of recombinant gene products to the central nervous system with nonautologous cells in alginate microcapsules.

Ross CJ, Ralph M, Chang PL.

Department of Biology, McMaster University, Hamilton, Ontario, Canada.

Somatic gene therapy using nonautologous recombinant cells immunologically protected with alginate microcapsules has been successfully used to treat rodent genetic diseases. We now report the delivery of recombinant gene products to the brain in rodents by implanting microencapsulated cells for the purpose of eventually treating neurodegenerative diseases with this technology. Alginate-poly-L-lysine-alginate microcapsules enclosing mouse C2C12 myoblasts expressing the marker gene human growth hormone (hGH) at 95+/-20 ng/million cells/hr were implanted into the right lateral ventricles of mice under stereotaxic guidance. Control mice were implanted similarly with nontransfected but encapsulated cells. Delivery of hGH to the different regions of the brain at various times postimplantation was examined. At 7, 28, 56, and 112 days postimplantation, hGH was detected at high levels around the implantation site and also at lower levels in the surrounding regions, while control mice showed no signal. Immunohistochemical staining of the implanted brains showed that on days 7, 56, and 112 postimplantation, hGH was localized in the tissues around the implantation site. Mice implanted with encapsulated but nontransfected cells showed no signal. Hence, the feasibility of using encapsulated nonautologous cells to deliver recombinant gene products to the brain for extended periods may allow the application of this technology to the treatment of neurodegenerative genetic disorders.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10022530&dopt=Abstract

Mol Cell Endocrinol. 1998 Nov 25;146(1-2):77-86.
Activation of the glycoprotein hormone alpha-subunit gene promoter in thyrotropes.

Sarapura VD, Strouth HL, Wood WM, Gordon DF, Ridgway EC.

Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA. virginia.sarapurchsc.edu

Pituitary expression of the glycoprotein hormone alpha-subunit gene localizes to thyrotropes and gonadotropes. Factors that activate the alpha-subunit promoter exclusively in thyrotropes have not been described. In the current studies, alpha-subunit promoter activity was compared in alphaTSH thyrotropic and alphaT3 gonadotropic cells. Deletional analysis revealed a more important contribution of the -453/-381 region in thyrotropic cells and the -341/-297 region in gonadotropic cells, while other deletions had similar effects. Mutational analysis revealed some regions that were functionally similar, while others were active only in thyrotropic cells, such as the regions - 434/ - 421, - 398/ - 385, - 376/- 364 and - 363/- 351, that decreased activity by approximately 2-fold each. Combined mutation of the regions - 434/ - 421, - 398/ - 385 and - 376/ - 364 decreased activity by 5-fold in thyrotropic cells and not at all in gonadotropic cells. Cotransfection with Ptx1 in CV-1 cells resulted in a strong stimulation of alpha-subunit promoter activity, that was significantly diminished with mutation of the - 398/ - 385 region that disrupts the Ptx1 binding site, suggesting that this factor may play a role in thyrotrope-specific activation. This analysis provides basic information important to identify common and unique factors contributing to the cell-specific expression of the alpha-subunit gene.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10022765&dopt=Abstract

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